endosymbiont reduction of host lipid synthesis and Stomoxyn-like peptide contribute to trypanosome resistance in the tsetse fly .

Tsetse flies ( spp.) vector African trypanosomes that cause devastating diseases in humans and domestic animals. Within the genus, species in the Palpalis subgroup exhibit greater resistance to trypanosome infections compared to those in the subgroup. Varying microbiota composition and species-specific genetic traits can significantly influence the efficiency of parasite transmission. Notably, infections with the endosymbiotic bacterium have been documented in several Palpalis subgroup species, including (). While infections in are known to hinder trypanosome transmission, the underlying mechanisms remain unknown. To investigate -mediated factors affecting vector competence, we conducted high-throughput RNA sequencing of the midgut tissue along with functional assays. Our findings reveal elevated oxidative stress in the midgut environment in the presence of , evidenced by increased expression of , which catalyzes the production of trypanocidal nitric oxide. Additionally, we observed impaired lipid biosynthesis leading to a reduction of this important class of nutrients essential for parasite and host physiologies. In contrast, trypanosome infections in midgut significantly upregulated various immunity-related genes, including a small peptide, , homologous to Stomoxyns first discovered in the stable fly . We observed that the locus is exclusive to the genomes of subgroup tsetse species. Stomoxyn is constitutively expressed in the cardia (proventriculus) and synthetic Stomoxyn exhibits potent activity against and bloodstream form of parasites, while showing no effect against insect stage procyclic forms or tsetse's commensal endosymbiont . Reducing Stomoxyn levels significantly increased trypanosome infection prevalence, indicating its potential trypanocidal role . Collectively, our results suggest that the enhanced resistance to trypanosomes observed in -infected may be due to the reduced lipid availability necessary for parasite metabolic maintenance. Furthermore, Stomoxyn could play a crucial role in the initial immune response(s) against mammalian parasites early in the infection process in the midgut and prevent gut colonization. We discuss the molecular characteristics of Stomoxyn, its spatial and temporal expression regulation and its microbicidal activity against parasites. Our findings reinforce the nutritional influences of microbiota on host physiology and host-pathogen dynamics.